Wnt16 regulates chondrocyte differentiation through Wnt/ planar cell polarity (PCP) pathway
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AbstractWnt signaling, a highly conserved signaling pathway, plays important roles in endochondral ossification which is a key process for skeletal development and bone repair. Wnt16, as one of the nineteen Wnt ligands, is reported to repress osteoclastogenesis, prevent cortical bone fragility fractures and to be upregulated in osteoarthritis. But how Wnt16 mediates chondrocyte differentiation during endochondral ossification is still unclear. Here, we investigate the roles of Wnt16 specifically in chondrocytes during endochondral ossification. First, we generated Col2a1-Wnt16 transgenic mice in which Wnt16 was overexpressed in chondrocytes under the control of Col2a1 promoter and enhancer. The transgenic mice showed a great reduction of tissue mineralization during embryonic development. We also genetically knocked out Wnt16 by generating Wnt16Loxp/Loxp;Col2a1-Cre mutant mice to examine whether Wnt16 is required for skeletal development. The mutant mice showed no severe phenotype in early skeletal development. However, after 2-month-old, the mutant mice displayed a smaller body size and lower bone mass as compared to that of control littermates. In vitro, our studies showed that Wnt16 delays chondrocyte hypertrophy and subsequent maturation. Mechanistically, we found that Wnt16 mainly activates the planar cell polarity (PCP) pathway through activation of JNK in primary chondrocyte. After treated chondroprogenitor cell line ATDC5 with SP600125, a JNK specific inhibitor, Wnt16-induced delay of chondrocyte hypertrophy is eliminated. In addition, our data suggest that Wnt16 mainly interacts with Ror2 or CD146, co-receptors of PCP pathway, but not Vangl2 or Ryk. Collectively, our current study provides evidence that Wnt16 delays chondrocyte hypertrophy through PCP pathway partially by binding to Ror2 and CD146. Our findings deepen the understanding of chondrocyte differentiation during endochondral ossification.
All Author(s) ListYelin ZENG, Wai YUENG, King Lun MAK, Hui ZHAO
Name of ConferenceExperimental Biology 2018
Start Date of Conference21/04/2018
End Date of Conference25/04/2018
Place of ConferenceSan Diego
Country/Region of ConferenceUnited States of America
Proceedings TitleFASEB JOURNAL
Year2018
Month4
Volume Number32
Issue NumberSupp 1
ISSN0892-6638
eISSN1530-6860
LanguagesEnglish-United States

Last updated on 2020-02-04 at 23:48